| Full text | |
| Author(s): |
Wilches-Buitrago, L.
[1, 2]
;
Viacava, P. R.
[1]
;
Cunha, F. Q.
[1]
;
Alves-Filho, J. C.
[1]
;
Fukada, S. Y.
[2]
Total Authors: 5
|
| Affiliation: | [1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil
[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ribeirao Preto - Brazil
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | Inflammation Research; v. 68, n. 5, p. 415-421, MAY 2019. |
| Web of Science Citations: | 0 |
| Abstract | |
Background Although some glycolytic intermediates have been shown to modulate several cell type formation and activation, the functional role of fructose 1,6-bisphosphate (FBP) on osteoclastogenesis is still unknown. Methods Osteoclastogenesis was evaluated on bone marrow preosteoclasts cultured with M-CSF -30 ng/ml, RANKL -10 ng/ml, and two concentrations of FBP (100 and 300 mu M). TRAP-positive stained cells were counted, and osteoclastogenic marker genes expression were evaluated by qPCR. Osteoclasts resorption capacity was evaluated by the expression of specific enzymes and capacity to resorb a mineralized matrix. The NF-kappa B activation was detected using RAW 264.7, stably expressing luciferase on the NF-B responsive promoter. Results We show that FBP, the product of the first stage of glycolysis, inhibited RANKL-induced osteoclasts differentiation and TRAP activity. The treatment of preosteoclasts with FBP attenuated osteoclast fusion and formation, without affecting cell viability. Moreover, the inhibition of several osteoclastogenic marker genes expression (TRAP, OSCAR, DC-STAMP, Integrin v, NFATc1) by FBP correlates with a reduction of mineralized matrix resorption capacity. The mechanism underlying FBP-inhibition of osteoclastogenesis involves NF-kappa B/NFATc1 signaling pathway inhibition. Conclusion Altogether these data show a protective role of a natural glycolytic intermediate in bone homeostasis that may have therapeutic benefit for osteolytic diseases. (AU) | |
| FAPESP's process: | 15/09034-0 - The role of O-glycosylation on the modulation of osteoclastogenesis and bone resorption |
| Grantee: | Sandra Yasuyo Fukada Alves |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/08216-2 - CRID - Center for Research in Inflammatory Diseases |
| Grantee: | Fernando de Queiroz Cunha |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |